This is a proposal to further examine the biochemistry, cell biology and pathogenesis of lipopolysaccharide binding protein (LBP) Dr. Tobias' thesis is that LBP assists in the clearance and detoxification of LPS and other microbial products. The following specific aims are listed. Specific Aim 1: to characterize the mechanism by which LBP enhances cellular uptake of LPS. This will be done by determining which pathways and molecules mediate cellular internalization of LPS. Specific Aim 2: to reinvestigate the role of LPB in the association of LPS with lipoproteins in normal and acute phase sera. This will be done by identifying and quantitating the interactions of LPS with the proteins of normal and LBP deficient sera and by studying the binding of LBP to normal and acute phase lipoproteins. Specific Aim 3: To characterize the role of LBP in clearance of LPS from the circulation of intact animals. This will be done by assessing the role of LBP in tissue and cellular targeting of LPS in normal and LBP knockout mice. Specific Aim 4: To establish the structural features of LBP important for formation of complexes with LPS and CD14. This will be done using LBP mutants, peptides derived from LPS, and anti-peptide antibodies.